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Preston was born and raised in Macon, Georgia. Her mother is an artist and art therapist, and her father is a geo-technical engineer. She began performing in community theater shows at age 8, and by age 12 she had begun her own front-yard theater company with other neighborhood kids.[2] Her brother is actor John G. Preston.

Preston has worked with her husband, actor Michael Emerson, on a number of projects. Emerson played Ben Linus on television's Lost, and Preston was a guest star in episode 20 of season 3, "The Man Behind the Curtain" as Ben's mother Emily in flashback scenes, though she and Emerson never shared scenes together. The couple were featured in the 2004 comedy film Straight-Jacket and the 2008 feature film, Ready? OK!. Most recently, she has appeared in several episodes of Person of Interest as Grace Hendricks, the former fiancée of Emerson's character, Harold Finch.

On September 6, 2013, it was announced that Preston had signed on to play a recurring character in the second season of the Kevin Bacon-led thriller, The Following; she portrayed Judy, a prostitute and ill-fated groupie of Joe Carroll. The show's second season premiered in January 2014.[9]